neutropenic sepsis: prevention and management of ... · features and using a validated risk scoring...

Neutropenic sepsis: prevention andmanagement of neutropenic sepsisin cancer patients

Issued: September 2012

NICE clinical guideline 151guidance.nice.org.uk/cg151

NICE has accredited the process used by the Centre for Clinical Practice at NICE to produceguidelines. Accreditation is valid for 5 years from September 2009 and applies to guidelines producedsince April 2007 using the processes described in NICE's 'The guidelines manual' (2007, updated2009). More information on accreditation can be viewed at www.nice.org.uk/accreditation

© NICE 2012

ContentsIntroduction .................................................................................................................................. 4

Patient-centred care ..................................................................................................................... 6

Terms used in this guideline ......................................................................................................... 7

Key priorities for implementation .................................................................................................. 8

Information, support and training ............................................................................................................ 8

Reducing the risk of septic complications of anticancer treatment ......................................................... 8

Managing suspected neutropenic sepsis in secondary and tertiary care................................................ 8

Managing confirmed neutropenic sepsis................................................................................................. 9

1 Guidance ................................................................................................................................... 11

1.1 Information, support and training ..................................................................................................... 11

1.2 Reducing the risk of septic complications of anticancer treatment ................................................... 11

1.3 When to refer patients in the community for suspected neutropenic sepsis ..................................... 12

1.4 Managing suspected neutropenic sepsis in secondary and tertiary care.......................................... 12

1.5 Managing confirmed neutropenic sepsis........................................................................................... 14

2 Notes on the scope of the guidance.......................................................................................... 17

3 Implementation ......................................................................................................................... 18

4 Research recommendations ..................................................................................................... 19

4.1 Service provision for neutropenic sepsis in patients with cancer ..................................................... 19

4.2 Patient support and information ........................................................................................................ 19

4.3 Signs and symptoms that predict neutropenic sepsis in the community ........................................... 20

4.4 Reducing the risk of complications of anticancer treatment in children and young people, and inadults diagnosed with lymphoma ............................................................................................................ 20

4.5 Switching from inpatient intravenous to outpatient oral antibiotic therapy in patients withneutropenic sepsis .................................................................................................................................. 21

5 Other versions of this guideline ................................................................................................. 22

5.1 Full guideline ..................................................................................................................................... 22

Neutropenic sepsis: prevention and management of neutropenicsepsis in cancer patients

NICE clinicalguideline 151

© NICE 2012. All rights reserved. Last modified September 2012 of 31

5.2 NICE pathway ................................................................................................................................... 22

5.3 Information for the public................................................................................................................... 22

6 Related NICE guidance............................................................................................................. 23

7 Advice from the Health Protection Agency ................................................................................ 25

Appendix A: The Guideline Development Group, National Collaborating Centre and NICEproject team.................................................................................................................................. 26

Guideline Development Group................................................................................................................ 26

National Collaborating Centre / Clinical Guideline Centre for Cancer..................................................... 27

NICE project team................................................................................................................................... 28

About this guideline ...................................................................................................................... 30




Introduction

Neutropenic sepsis is a potentially fatal complication of anticancer treatment (particularlychemotherapy). Mortality rates ranging between 2% and 21% have been reported in adults.Aggressive use of inpatient intravenous antibiotic therapy has reduced morbidity and mortalityrates and intensive care management is now needed in fewer than 5% of cases in England.

Systemic therapies to treat cancer can suppress the ability of bone marrow to respond toinfection. This is particularly the case with systemic chemotherapy, although radiotherapy canalso cause such suppression.

Chemotherapy is most commonly given in a day-case or outpatient setting so most episodes ofobvious sepsis, and fever in a person with potential sepsis, present in the community. Peoplereceiving chemotherapy and their carers need to be told about the risk of neutropenic sepsis andthe warning signs and symptoms. Neutropenic sepsis is a medical emergency that requiresimmediate hospital investigation and treatment.

A report by the National Confidential Enquiry into Patient Outcome and Death (Systemic anti-cancer therapy: for better for worse? [2008]) and a follow-up report by the NationalChemotherapy Advisory Group (Chemotherapy services in England: ensuring quality and safety[2010]) highlighted problems in the management of neutropenic sepsis in adults receivingchemotherapy. These problems included inadequate management of neutropenic fever leadingto avoidable deaths, and a need for systems for urgent assessment and organisation-levelpolicies for dealing with neutropenic fever. The reports also noted variation in the provision ofinformation on the treatment of side effects and on access to 24-hour telephone advice.

In addition, there is national variation in the use of:

primary and secondary prophylaxis

risk stratification in episodes of febrile neutropenia

oral or intravenous antibiotics

growth factors

inpatient or outpatient management policies.




http://publications.nice.org.uk/neutropenic-sepsis-prevention-and-management-of-neutropenic-sepsis-in-cancer-patients-cg151/terms-used-in-this-guideline

http://www.ncepod.org.uk/2008sact.htm

http://www.ncepod.org.uk/2008sact.htm

http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/DH_104500

This guideline aims to improve outcomes by providing evidence-based recommendations on theprevention, identification and management of this life-threatening complication of cancertreatment.

The guideline will assume that prescribers will use a drug's summary of product characteristics toinform decisions made with individual patients.

This guideline recommends some drugs for indications for which they do not have a UKmarketing authorisation at the date of publication, if there is good evidence to support that use.The prescriber should follow relevant professional guidance, taking full responsibility for thedecision. The patient (or their parent or carer) should provide informed consent, which should bedocumented. See the General Medical Council's Good practice in prescribing medicines –guidance for doctors and the prescribing advice provided by the Joint Standing Committee onMedicines (a joint committee of the Royal College of Paediatrics and Child Health and theNeonatal and Paediatric Pharmacists Group) for further information. Where recommendationshave been made for the use of drugs outside their licensed indications ('off-label use'), thesedrugs are marked with a footnote in the recommendations.




http://www.gmc-uk.org/guidance/ethical_guidance/14316.asp


http://www.rcpch.ac.uk/child-health/childrens-medicines/childrens-medicines#Unlicensed_medicines_statement

Patient-centred care

This guideline offers best practice advice on the care of children, young people and adults havinganticancer treatment.

Treatment and care should take into account patients' needs and preferences. Patients shouldhave the opportunity to make informed decisions about their care and treatment, in partnershipwith their healthcare professionals. If patients do not have the capacity to make decisions,healthcare professionals should follow the Department of Health's advice on consent and thecode of practice that accompanies the Mental Capacity Act. In Wales, healthcare professionalsshould follow advice on consent from the Welsh Government.

If the patient is under 16, healthcare professionals should follow the guidelines in Seekingconsent: working with children.

Good communication between healthcare professionals and patients is essential. It should besupported by evidence-based written information tailored to the person's needs. Treatment andcare, and the information people are given about it, should be culturally appropriate. It shouldalso be accessible to people with additional needs such as physical, sensory or learningdisabilities, and to people who do not speak or read English.

If the patient agrees, families and carers should have the opportunity to be involved in decisionsabout treatment and care.

Families and carers should also be given the information and support they need.

Care of young people in transition between paediatric and adult services should be planned andmanaged according to the best practice guidance described in the Department of Health'sTransition: getting it right for young people.

Adult and paediatric healthcare teams should work jointly to provide assessment and services toyoung people having anticancer treatment. Diagnosis and management should be reviewedthroughout the transition process, and there should be clarity about who is the lead clinician toensure continuity of care.




https://www.gov.uk/government/publications/reference-guide-to-consent-for-examination-or-treatment-second-edition

http://www.justice.gov.uk/protecting-the-vulnerable/mental-capacity-act

http://www.wales.nhs.uk/consent

http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyandGuidance/DH_4007005

http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyandGuidance/DH_4007005

http://webarchive.nationalarchives.gov.uk/20130107105354/http:/www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4132145

Terms used in this guideline

Anticancer treatment Treatment that is given with the intent to reduce the level of cancer cellsin a patient. It includes, but is not limited to, chemotherapy and radiotherapy.

Empiric An action undertaken prior to determination of the underlying cause of a problem.

Empiric antibiotic An antibiotic given to a person before a specific microorganism or source ofthe potential infection is known. It is usually a broad-spectrum antibiotic and the treatment maychange if the microorganism or source is confirmed.

G-CSF (granulocyte-colony stimulating factor) A type of protein that stimulates the bonemarrow to make white blood cells (granulocytes).




Key priorities for implementation

The following recommendations have been identified as priorities for implementation.

Information, support and training

Information and support for patients and carers

Provide patients having anticancer treatment and their carers with written and oralinformation, both before starting and throughout their anticancer treatment, on:

neutropenic sepsis

how and when to contact 24-hour specialist oncology advice

how and when to seek emergency care.

Reducing the risk of septic complications of anticancertreatment

For adult patients (aged 18 years and older) with acute leukaemias, stem cell transplants orsolid tumours in whom significant neutropenia (neutrophil count 0.5×109 per litre or lower) isan anticipated consequence of chemotherapy, offer prophylaxis with a fluoroquinoloneduring the expected period of neutropenia only.

Managing suspected neutropenic sepsis in secondary andtertiary care

Emergency treatment and assessment

Treat suspected neutropenic sepsis as an acute medical emergency and offer empiricantibiotic therapy immediately.

Include in the initial clinical assessment of patients with suspected neutropenic sepsis:

history and examination







full blood count, kidney and liver function tests (including albumin),C-reactive protein, lactate and blood culture.

Starting antibiotic therapy

All patients

Offer beta lactam monotherapy with piperacillin with tazobactam[1] as initial empiric antibiotictherapy to patients with suspected neutropenic sepsis who need intravenous treatmentunless there are patient-specific or local microbiological contraindications.

Do not offer an aminoglycoside, either as monotherapy or in dual therapy, for the initialempiric treatment of suspected neutropenic sepsis unless there are patient-specific or localmicrobiological indications.

Confirming a diagnosis of neutropenic sepsis

Diagnose neutropenic sepsis in patients having anticancer treatment whose neutrophil countis 0.5 × 109 per litre or lower and who have either:

a temperature higher than 38oC or

other signs or symptoms consistent with clinically significant sepsis.

Managing confirmed neutropenic sepsis

Assessing the patient's risk of septic complications

A healthcare professional with competence in managing complications of anticancertreatment should assess the patient's risk of septic complications within 24 hours ofpresentation to secondary or tertiary care, basing the risk assessment on presentationfeatures and using a validated risk scoring system[2].

Patients at low risk of septic complications

Consider outpatient antibiotic therapy for patients with confirmed neutropenic sepsis and alow risk of developing septic complications, taking into account the patient's social andclinical circumstances and discussing with them the need to return to hospital promptly if aproblem develops.





Patients at high risk of septic complications

Offer discharge to patients having empiric antibiotic therapy for neutropenic sepsis onlyafter:

the patient's risk of developing septic complications has been reassessed as low by ahealthcare professional with competence in managing complications of anticancertreatment using a validated risk scoring system[2]and

taking into account the patient's social and clinical circumstances and discussing withthem the need to return to hospital promptly if a problem develops.

[1] At the time of publication (September 2012) piperacillin with tazobactam did not have a UKmarketing authorisation for use in children aged under 2 years. The prescriber should followrelevant professional guidance, taking full responsibility for the decision. The child's parent orcarer should provide informed consent, which should be documented. See the General MedicalCouncil's Good practice in prescribing medicines – guidance for doctors and the prescribingadvice provided by the Joint Standing Committee on Medicines (a joint committee of the RoyalCollege of Paediatrics and Child Health and the Neonatal and Paediatric Pharmacists Group) forfurther information.

[2] Examples of risk scoring systems include The Multinational Association for Supportive Care inCancer risk index: a multinational scoring system for identifying low-risk febrile neutropeniccancer patients (Journal of Clinical Oncology 2000; 18: 3038–51]) and the modified Alexanderrule for children (aged under 18) (European Journal of Cancer 2009; 45: 2843–9).





http://www.rcpch.ac.uk/child-health/childrens-medicines/childrens-medicines


http://jco.ascopubs.org/content/18/16/3038.full.pdf



http://www.ejcancer.info/article/S0959-8049(09)00432-8/abstract


1 Guidance

The following guidance is based on the best available evidence. The full guideline gives detailsof the methods and the evidence used to develop the guidance.

The recommendations in this guideline were developed after discussion of the relevance of theevidence to children, young people and adults with cancer. The recommendations are intendedfor use in patients of any age. Where age-limited or disease-specific recommendations are madethey are clearly indicated as such.

1.1 Information, support and training

1.1.1 Information and support for patients and carers

1.1.1.1 Provide patients having anticancer treatment and their carers with written andoral information, both before starting and throughout their anticancer treatment,on:

neutropenic sepsis

how and when to contact 24-hour specialist oncology advice

how and when to seek emergency care.

1.1.2 Training for healthcare professionals

1.1.2.1 Healthcare professionals and staff who come into contact with patients havinganticancer treatment should be provided with training on neutropenic sepsis.The training should be tailored according to the type of contact.

1.2 Reducing the risk of septic complications of anticancertreatment

1.2.1.1 For adult patients (aged 18 years and older) with acute leukaemias, stem celltransplants or solid tumours in whom significant neutropenia (neutrophil count0.5×109 per litre or lower) is an anticipated consequence of chemotherapy,




http://guidance.nice.org.uk/CG151/Guidance


offer prophylaxis with a fluoroquinolone during the expected period ofneutropenia only.

1.2.1.2 Rates of antibiotic resistance and infection patterns should be monitored intreatment facilities where patients are having fluoroquinolones for theprophylaxis of neutropenic sepsis[3].

1.2.1.3 Do not routinely offer G-CSF for the prevention of neutropenic sepsis in adultsreceiving chemotherapy unless they are receiving G-CSF as an integral part ofthe chemotherapy regimen or in order to maintain dose intensity.

1.3 When to refer patients in the community for suspectedneutropenic sepsis

1.3.1.1 Suspect neutropenic sepsis in patients having anticancer treatment whobecome unwell.

1.3.1.2 Refer patients with suspected neutropenic sepsis immediately for assessmentin secondary or tertiary care.

1.4 Managing suspected neutropenic sepsis in secondaryand tertiary care

1.4.1 Emergency treatment and assessment

1.4.1.1 Treat suspected neutropenic sepsis as an acute medical emergency and offerempiric antibiotic therapy immediately.

1.4.1.2 Include in the initial clinical assessment of patients with suspected neutropenicsepsis:

history and examination

full blood count, kidney and liver function tests (including albumin), C-reactiveprotein, lactate and blood culture.







1.4.2 Further assessment

1.4.2.1 After completing the initial clinical assessment (see recommendation 1.4.1.2)try to identify the underlying cause of the sepsis by carrying out:

additional peripheral blood culture in patients with a central venous access device ifclinically feasible

urinalysis in all children aged under 5 years.

1.4.2.2 Do not perform a chest X-ray unless clinically indicated.

1.4.3 Starting antibiotic therapy

All patients

1.4.3.1 Offer beta lactam monotherapy with piperacillin with tazobactam[4] as initialempiric antibiotic therapy to patients with suspected neutropenic sepsis whoneed intravenous treatment unless there are patient-specific or localmicrobiological contraindications.

1.4.3.2 Do not offer an aminoglycoside, either as monotherapy or in dual therapy, forthe initial empiric treatment of suspected neutropenic sepsis unless there arepatient-specific or local microbiological indications.

Empiric glycopeptide antibiotics in patients with central venous accessdevices

1.4.3.3 Do not offer empiric glycopeptide antibiotics to patients with suspectedneutropenic sepsis who have central venous access devices unless there arepatient-specific or local microbiological indications.

1.4.3.4 Do not remove central venous access devices as part of the initial empiricmanagement of suspected neutropenic sepsis.





1.4.4 Confirming a diagnosis of neutropenic sepsis

1.4.4.1 Diagnose neutropenic sepsis in patients having anticancer treatment whoseneutrophil count is 0.5×109 per litre or lower and who have either:

a temperature higher than 38oC or

other signs or symptoms consistent with clinically significant sepsis.

1.5 Managing confirmed neutropenic sepsis

1.5.1 Assessing the patient's risk of septic complications

1.5.1.1 A healthcare professional with competence in managing complications ofanticancer treatment should assess the patient's risk of septic complicationswithin 24 hours of presentation to secondary or tertiary care, basing the riskassessment on presentation features and using a validated risk scoringsystem[5].

1.5.2 Patients at low risk of septic complications

1.5.2.1 Consider outpatient antibiotic therapy for patients with confirmed neutropenicsepsis and a low risk of developing septic complications, taking into accountthe patient's social and clinical circumstances and discussing with them theneed to return to hospital promptly if a problem develops.

1.5.3 Patients at high risk of septic complications

1.5.3.1 For patients with confirmed neutropenic sepsis and a high risk of developingseptic complications, a healthcare professional with competence in managingcomplications of anticancer treatment should daily:

review the patient's clinical status

reassess the patient's risk of septic complications, using a validated risk scoringsystem[5].






1.5.3.2 Do not switch initial empiric antibiotics in patients with unresponsive feverunless there is clinical deterioration or a microbiological indication.

1.5.3.3 Switch from intravenous to oral antibiotic therapy after 48 hours of treatment inpatients whose risk of developing septic complications has been reassessedas low by a healthcare professional with competence in managingcomplications of anticancer treatment using a validated risk scoring system[5].

1.5.3.4 Offer discharge to patients having empiric antibiotic therapy for neutropenicsepsis only after:

the patient's risk of developing septic complications has been reassessed as low bya healthcare professional with competence in managing complications of anticancertreatment using a validated risk scoring system[5]and

taking into account the patient's social and clinical circumstances and discussingwith them the need to return to hospital promptly if a problem develops.

1.5.4 Duration of empiric antibiotic treatment

1.5.4.1 Continue inpatient empiric antibiotic therapy in all patients who haveunresponsive fever unless an alternative cause of fever is likely.

1.5.4.2 Discontinue empiric antibiotic therapy in patients whose neutropenic sepsishas responded to treatment, irrespective of neutrophil count.

[3] For more information see the Department of Health's Updated guidance on the diagnosis andreporting of Clostridium difficile and guidance from the Health Protection Agency and theDepartment of Health on Clostridium difficile infection: how to deal with the problem.

[4] At the time of publication (September 2012) piperacillin with tazobactam did not have a UKmarketing authorisation for use in children aged under 2 years. The prescriber should followrelevant professional guidance, taking full responsibility for the decision. The child's parent orcarer should provide informed consent, which should be documented. See the General MedicalCouncil's Good practice in prescribing medicines – guidance for doctors and the prescribingadvice provided by the Joint Standing Committee on Medicines (a joint committee of the Royal





https://www.gov.uk/government/publications/updated-guidance-on-the-diagnosis-and-reporting-of-clostridium-difficile


http://www.hpa.org.uk/consultations/2008/cdiff.htm




College of Paediatrics and Child Health and the Neonatal and Paediatric Pharmacists Group) forfurther information.

.

[5] Examples of risk scoring systems include the Multinational Association for Supportive Care inCancer risk index: a multinational scoring system for identifying low-risk febrile neutropeniccancer patients (Journal of Clinical Oncology 2000; 18: 3038–51) and the modified Alexanderrule for children (aged under 18) (European Journal of Cancer 2009; 45: 2843–9).









2 Notes on the scope of the guidance

NICE guidelines are developed in accordance with a scope that defines what the guideline willand will not cover.

Groups that are covered

Children, young people and adults with cancer (haematological and solid tumourmalignancies) receiving anticancer treatment.

No subgroups needing special consideration have been identified.

Groups that are not covered

Children, young people and adults with neutropenia or neutropenic sepsis not caused byanticancer treatment.

How this guideline was developed

NICE commissioned the National Collaborating Centre for Cancer to develop this guideline.The Centre established a Guideline Development Group (see appendix A), which reviewedthe evidence and developed the recommendations.

There is more information about how NICE clinical guidelines are developed on the NICEwebsite. See also NICE's How NICE clinical guidelines are developed: an overview forstakeholders, the public and the NHS.




http://guidance.nice.org.uk/CG/Wave23/11/Scope

http://publications.nice.org.uk/neutropenic-sepsis-prevention-and-management-of-neutropenic-sepsis-in-cancer-patients-cg151/appendix-a-the-guideline-development-group-national-collaborating-centre-and-nice-project-team

http://www.nice.org.uk/HowWeWork

http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/developing_nice_clinical_guidelines.jsp?domedia=1&mid=62F02D9B-19B9-E0B5-D4A26EC9A934FDC7

http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/developing_nice_clinical_guidelines.jsp?domedia=1&mid=62F02D9B-19B9-E0B5-D4A26EC9A934FDC7

3 Implementation

NICE has developed tools to help organisations implement this guidance.




http://guidance.nice.org.uk/CG151

4 Research recommendations

The Guideline Development Group has made the following recommendations for research,based on its review of evidence, to improve NICE guidance and patient care in the future.

4.1 Service provision for neutropenic sepsis in patients withcancer

A prospective national cohort study should be carried out to assess the incidence of suspectedand proven neutropenic sepsis in patients having anticancer treatment.

Why this is important

The incidence of suspected neutropenic sepsis in England and Wales is difficult to determine. Anational cohort study of patients referred for suspected neutropenic sepsis, including diagnosesand clinical outcomes, should be undertaken to improve service planning and delivery. Such astudy may also generate hypotheses concerning more and less efficient methods of deliveringservices for neutropenic sepsis, which could then be formally tested.

4.2 Patient support and information

A descriptive study involving patients who have had neutropenic sepsis and their carers shouldbe undertaken to find out what types of support and information patients and carers were given,which of these they found helpful or unhelpful, and whether they think additional or differenttypes of support or information are needed.


There is a lack of research on the experience of patients who have had neutropenic sepsis andtheir carers. Better knowledge of the support and information patients and carers are given, howhelpful they find it and how they think it could be improved will allow the development of differentapproaches to providing information and support and test these in practice. This research couldimprove the experience of patients, and potentially their clinical outcomes. It may also highlightimportant inequities and suggest ways of addressing them.





4.3 Signs and symptoms that predict neutropenic sepsis inthe community

A prospective study should be carried out to determine which signs and symptoms experiencedby patients in the community predict neutropenic sepsis and the outcomes of these episodes.


The initial decision to refer to secondary or tertiary care for investigation for suspectedneutropenic sepsis is an important step that has both risks and benefits. An overly inclusiveapproach will inconvenience many patients and carers, expose patients to unnecessary invasivetesting and increase resource use by the health service. Referral criteria that are too narrow willdelay the emergency treatment of infection and may lead to death, increased need for intensiveor critical care facilities, and reduced overall quality of life for patients with cancer and theircarers. The current research base in this area is weak and largely extrapolated from selectedpopulations in hospitals. A clearer, quantitative understanding of how the features of neutropenicsepsis appear in patients may lead to more accurate referral criteria for suspected neutropenicsepsis.

4.4 Reducing the risk of complications of anticancertreatment in children and young people, and in adultsdiagnosed with lymphoma

Randomised studies should investigate primary prophylaxis of neutropenic sepsis in2 populations: children and young people (aged under 18) having treatment for solid tumours orhaematological malignancies, or stem cell transplantation; and adults (aged 18 and older)diagnosed with lymphoma. The studies should compare the effectiveness of fluoroquinoloneantibiotics given alone, fluoroquinolone antibiotics given together with G-CSF preparations, andG-CSF preparations given alone. Outcome measures should include overall mortality, infectiousepisodes and adverse events. In addition, quality of life should be determined using quantitativeand qualitative methods. The resulting data should be used to develop a cost-effectivenessanalysis comparing these 3 forms of prophylaxis in children and young people having anticancertreatment, and in adults diagnosed with lymphoma.






Data from studies of adults with leukaemia, stem cell transplantation and many solid tumourssuggest that prophylaxis with fluoroquinolone antibiotics reduces the risk of neutropenic sepsis.However, the benefit of fluoroquinolone antibiotics in adults diagnosed with lymphoma is unclear.Children and young people having anticancer treatment are a distinct population and differ fromadults in a number of ways, including the types of cancer they have, the anticancer treatmentthey are given, their reactions to fluoroquinolones and subcutaneous injections, and the easewith which they can adhere to daily medication. The effects of these differences are not known,but it is known that death rates from neutropenic sepsis are higher in children and young peoplethan in adults. Studies of primary prophylaxis of neutropenic sepsis in children and young adults,and in adults with lymphoma, could be of great value in helping to reduce the risk of neutropenicsepsis in these 2 patient populations.

4.5 Switching from inpatient intravenous to outpatient oralantibiotic therapy in patients with neutropenic sepsis

A randomised controlled trial should be undertaken to evaluate the clinical and cost effectivenessof stopping intravenous antibiotic therapy and switching to oral therapy within the first 24 hours oftreatment in patients with neutropenic sepsis who are having treatment with intravenousantibiotics. The outcomes to be measured are overtreatment, death, need for critical care, lengthof hospital stay, duration of fever and quality of life.


Moderately strong evidence was found to support the use of outpatient therapies for patients withneutropenic sepsis who are at low risk of severe infection. These studies switched from inpatientto outpatient treatment at a variety of time points. A meta-regression undertaken by the GuidelineDevelopment Group suggested that very early (before 24 hours) discharge is associated with agreater risk of readmission and need to change treatments, but the evidence was sparse. If ashort period of hospital admission was found to be safe and effective for selected patients withneutropenic sepsis, it could provide considerable improvements in their quality of life and reducethe resource burden on hospitals.




5 Other versions of this guideline

5.1 Full guideline

The full guideline, Neutropenic sepsis: prevention and management of neutropenic sepsis incancer patients, contains details of the methods and evidence used to develop the guideline. It ispublished by the National Collaborating Centre for Cancer.

5.2 NICE pathway

The recommendations from this guideline have been incorporated into a NICE pathway.

5.3 Information for the public

NICE has produced information for the public explaining this guideline.

We encourage NHS and voluntary sector organisations to use text from this information in theirown materials.






http://pathways.nice.org.uk/pathways/neutropenic-sepsis

http://publications.nice.org.uk/IFP151

6 Related NICE guidance

Published

Patient experience in adult NHS services. NICE clinical guideline 138 (2012).

Colorectal cancer. NICE clinical guideline 131 (2011).

Ovarian cancer. NICE clinical guideline 122 (2011).

Lung cancer. NICE clinical guideline 121 (2011).

Metastatic malignant disease of unknown primary origin. NICE clinical guideline 104 (2010).

Advanced breast cancer. NICE clinical guideline 81 (2009).

Early and locally advanced breast cancer. NICE clinical guideline 80 (2009).

Medicines adherence. NICE clinical guideline 76 (2009).

Prostate cancer. NICE clinical guideline 58 (2008).

Acutely ill patients in hospital. NICE clinical guideline 50 (2007).

Improving outcomes for people with brain and other CNS tumours. NICE cancer serviceguidance (2006).

Improving outcomes for people with sarcoma. NICE cancer service guidance (2006).

Improving outcomes for people with skin tumours including melanoma. NICE cancer serviceguidance (2006).

Improving outcomes in children and young people with cancer. NICE cancer serviceguidance (2005).

Improving outcomes in colorectal cancers. NICE cancer service guidance (2004).

Improving outcomes in head and neck cancers. NICE cancer service guidance (2004).

Improving supportive and palliative care for adults with cancer. NICE cancer serviceguidance (2004).




http://guidance.nice.org.uk/cg138










http://guidance.nice.org.uk/CSGBrainCNS

http://guidance.nice.org.uk/CSGsarcoma

http://guidance.nice.org.uk/CSGSTIM

http://guidance.nice.org.uk/CSGCYP

http://guidance.nice.org.uk/CSGCC

http://guidance.nice.org.uk/CSGHN

http://guidance.nice.org.uk/CSGSP

Improving outcomes in haematological cancers. NICE cancer service guidance (2003).

Improving outcomes in breast cancer. NICE cancer service guidance (2002).

Improving outcomes in urological cancers. NICE cancer service guidance (2002).

Improving outcomes in upper gastro-intestinal cancers. Service guidance (2001).

Improving outcomes in gynaecological cancers. Service guidance (1999).

Improving outcomes in lung cancer. Service guidance (1998).

Under development

NICE is developing the following guidance (details available from the NICE website):

Familial breast cancer. NICE clinical guideline. Publication expected April 2013.

Prostate cancer. NICE clinical guideline. Publication expected November 2013.

Referral for suspected cancer. NICE clinical guideline. Publication date to be confirmed.

Bladder cancer. NICE clinical guideline. Publication expected September 2014.




http://guidance.nice.org.uk/CSGHO

http://guidance.nice.org.uk/CSGBC

http://guidance.nice.org.uk/CSGUC

http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4010025



http://www.nice.org.uk/

http://guidance.nice.org.uk/index.jsp?action=byId&o=13583

http://guidance.nice.org.uk/CG/Wave0/618

http://guidance.nice.org.uk/CG/Wave0/600

7 Advice from the Health Protection Agency

The Health Protection Agency has provided the following advice about NICE's recommendationon reducing the risk of septic complications of anticancer treatment (see recommendation1.2.1.1).

Fluoroquinolone prophylaxis is advocated as beneficial for some patients with neutropenia (seeAntibiotic prophylaxis in neutropenic patients: new evidence, practical decisions). However, itraises 2 concerns:

fluoroquinolone prophylaxis can contribute to selection of resistance, particularly inEnterobacteriaceae

fluoroquinolones are associated with the selection of Clostridium difficile.

Attention should be paid to both risks.

Colonisation with resistant Enterobacteriaceae should be examined at induction of neutropeniaand weekly thereafter until prophylaxis is stopped. The easiest method is to plate a rectal swab,or faeces, onto MacConkey agar, and to place a 1 mg (that is, standard) ciprofloxacin disc on thefirst series of streaks after the inoculum pool. After incubation the plate should be examined forbacterial colonies within the inhibition zone. If growth is found, the bacteria should be identifiedand their antibiograms determined, since many fluoroquinolone-resistant isolates are resistant tomultiple other agents. The results should inform initial empiric therapy if the patient experiencesa subsequent febrile episode. Time trends in resistance should be monitored, both in individualpatients and within units.

Advice on the diagnosis of Clostridium difficile-related disease is provided in Updated guidanceon the diagnosis and reporting of Clostridium difficile. This advice should be followed for patientswith symptoms of diarrhoea.




http://publications.nice.org.uk/neutropenic-sepsis-prevention-and-management-of-neutropenic-sepsis-in-cancer-patients-cg151/guidance#reducing-the-risk-of-septic-complications-of-anticancer-treatment-2

http://publications.nice.org.uk/neutropenic-sepsis-prevention-and-management-of-neutropenic-sepsis-in-cancer-patients-cg151/guidance#reducing-the-risk-of-septic-complications-of-anticancer-treatment-2

http://www.ncbi.nlm.nih.gov/pubmed/16977651



Appendix A: The Guideline Development Group, NationalCollaborating Centre and NICE project team

Guideline Development Group

Professor Barry W Hancock OBEEmeritus Professor of Oncology, University of Sheffield

Dr Robert S PhillipsConsultant Paediatric and Teenage/Young Adult Oncologist (Locum), Leeds General Infirmary

Mrs Wendy KingMacmillan Paediatric Oncology Clinical Nurse Specialist[6], Whittington Health, London

Dr Barbara Anne CrosseConsultant Medical Oncologist, Calderdale and Huddersfield NHS Foundation Trust

Dr Mark HollandConsultant Physician in Acute Medicine, University Hospital of South Manchester NHSFoundation Trust[7]

Catherine OakleyChemotherapy Nurse Consultant, Guy's and St Thomas' NHS Foundation Trust, London

Professor Rosemary A BarnesProfessor/Honorary Consultant Medical Microbiologist, Cardiff University, School of Medicine/University Hospital of Wales

Mrs Anne HigginsHaemato-oncology Clinical Nurse Specialist and South West London Cancer Network LeadChemotherapy Nurse, Epsom and St Helier University NHS Trust

Dr Peter JenkinsConsultant Clinical Oncologist, Cheltenham General Hospital




Dr Anton KrugerConsultant Haematologist, Royal Cornwall Hospital

Dr Paul D WallmanConsultant in Emergency Medicine, Brighton and Sussex University Hospitals

Mrs Jeanette HawkinsLead Cancer Nurse, Birmingham Children's Hospital NHS Foundation Trust

Dr Helen Clayson[8]

Medical Director[9], St Mary's Hospice, Cumbria

Miss Miranda HolmesService Improvement, East Midlands Cancer Network

Dr Anne DavidsonConsultant Paediatrician with an interest in Oncology, Royal Alexandra Children's Hospital,Brighton

Ms Janie Thomas[10]

Patient and carer member

Dr Nicola HarrisPatient and carer member

Miss Rachel DrewPatient and carer member

National Collaborating Centre / Clinical Guideline Centre forCancer

Dr John GrahamDirector

Dr Andrew ChampionCentre Manager




Angela BennettAssistant Centre Manager

Lianne GwillimProject Manager

Dr Nathan Bromham, Dr Karen Francis, Dr Mia Schmidt-Hansen, Dr Catrin LewisReviewers

Sabine Berendse, Stephanie ArnoldInformation Specialists

Huajie Jin, Dr Alec MinersHealth Economists

Dr Timothy SimmonsNeeds Assessment

NICE project team

Sharon Summers-MaAssociate Director

Claire TurnerGuideline Commissioning Manager

Anthony GildeaGuideline Coordinator

Judith ThorntonTechnical Lead

Jasdeep HayreHealth Economist




Judy McBrideEditor

[6] From March 2012, job title changed to Macmillan Paediatric Oncology Nurse Consultant

[7] From May 2012, place of work changed to Salford Royal NHS Foundation Trust

[8] GP principal from 1980 to 2005

[9] Retired March 2011

[10] From September 2010 – RIP December 2011




About this guideline

NICE clinical guidelines are recommendations about the treatment and care of people withspecific diseases and conditions in the NHS in England and Wales.

The guideline was developed by the National Collaborating Centre for Cancer, which is based atthe Velindre NHS Trust. The Collaborating Centre worked with a group of healthcareprofessionals (including consultants, GPs and nurses), patients and carers, and technical staff,who reviewed the evidence and drafted the recommendations. The recommendations werefinalised after public consultation.

The methods and processes for developing NICE clinical guidelines are described in Theguidelines manual.

The recommendations from this guideline have been incorporated into a NICE pathway. Wehave produced information for the public explaining this guideline. Tools to help you put theguideline into practice and information about the evidence it is based on are also available.

Changes after publicationJuly 2013: minor maintenance

Your responsibilityThis guidance represents the view of NICE, which was arrived at after careful consideration ofthe evidence available. Healthcare professionals are expected to take it fully into account whenexercising their clinical judgement. However, the guidance does not override the individualresponsibility of healthcare professionals to make decisions appropriate to the circumstances ofthe individual patient, in consultation with the patient and/or guardian or carer, and informed bythe summary of product characteristics of any drugs they are considering.

Implementation of this guidance is the responsibility of local commissioners and/or providers.Commissioners and providers are reminded that it is their responsibility to implement theguidance, in their local context, in light of their duties to avoid unlawful discrimination and to haveregard to promoting equality of opportunity. Nothing in this guidance should be interpreted in away that would be inconsistent with compliance with those duties.




http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/clinicalguidelinedevelopmentmethods/clinical_guideline_development_methods.jsp

http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/clinicalguidelinedevelopmentmethods/clinical_guideline_development_methods.jsp

http://pathways.nice.org.uk/neutropenic-sepsis

http://publications.nice.org.uk/IFP151


Copyright© National Institute for Health and Clinical Excellence 2012. All rights reserved. NICE copyrightmaterial can be downloaded for private research and study, and may be reproduced foreducational and not-for-profit purposes. No reproduction by or for commercial organisations, orfor commercial purposes, is allowed without the written permission of NICE.

Contact NICENational Institute for Health and Clinical ExcellenceLevel 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT

www.nice.org.uk

[email protected]

0845 003 7780




nice.nhs.uk/Data/Communications/Publishing 2/Clinical Guidelines/Neutropenic sepsis/Publication/www.nice.org.uk

nice.nhs.uk/Data/Communications/Publishing 2/Clinical Guidelines/Neutropenic sepsis/Publication/[email protected]

neutropenic sepsis: prevention and management of ... · features and using a validated risk scoring...

Documents